Method and apparatus for locating the fossa ovalis and performing transseptal puncture

ABSTRACT

A method of identifying the fossa ovalis in a patient by positioning one or more electrodes against the tissue of the interatrial septum of the patient and acquiring unipolar and/or bipolar electrograms of the tissue of the interatrial septum while moving the electrodes to a plurality of positions against the tissue of the interatrial septum. The fossa ovalis is identified on the basis of unipolar voltage reduction, signal fractionation, broadened signal, reduced signal slew rate, reduced local myocardial impedance, increased phase angle and/or increased pacing threshold. An apparatus for identify the fossa ovalis is also provided.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of U.S. Provisional Application No.60/405,849, filed Aug. 24, 2002 which is hereby incorporated byreference.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates to methods and apparatus for locating thefossa ovalis, as well as methods and apparatus for performingtransseptal punctures.

2. Description of Related Art

The transseptal puncture for left atrial and left ventricularcatheterization was initially described simultaneously by Ross and Copein 1959. In the 1960s, Brockenbrough and colleagues modified the designof the transseptal needle and the guiding catheter. In the late 1960sand 70s, its use declined because of the occurrence of complications andbecause of the development of selective coronary arteriography which ledto the refinement of catheterization of the left side of the heart bythe retrograde approach. With the advent of percutaneous balloon mitralvalvuloplasty, antegrade percutaneous aortic valvuloplasty as well ascatheter ablation of arrhythmias arising from the left atrium (orutilizing left sided bypass tracts), the transseptal puncture techniquefor access to the left atrium and ventricle has made a strong comeback.

The goal of transseptal catheterization is to cross from the rightatrium to the left atrium through the fossa ovalis. Mechanical punctureof this area with a needle and catheter combination is required for theprocedure. Typically, a guidewire is inserted through the right femoralvein and advanced to the superior vena cava. A sheath (typically about66 cm long) is placed over a dilator (typically about 70 cm long) thatis advanced over the guidewire into the superior vena cava. Theguidewire is then removed and a 71 cm Brockenbrough needle is advancedup to the dilator tip. The apparatus is dragged down into the rightatrium, along the septum. When the dilator tip is positioned adjacentthe fossa ovalis (some times determined under ultrasound guidance), theneedle is then pushed forward so that it extends past the dilator tip,through the fossa ovalis into the left atrium. The dilator and sheathmay then be pushed through the fossa ovalis over the needle. The dilatorand needle are then removed, leaving the sheath in place in the leftatrium. Thereafter, catheters may be inserted through the sleeve intothe left atrium in order to perform various necessary procedures.

The danger of the transseptal approach lies in the possibility that theneedle and catheter will puncture an adjacent structure such as theaorta, the coronary sinus or the free wall of the atrium. In theCooperative study on Cardiac Catheterization, a 0.2% mortality rate, 6%incidence rate of major complications and 3.4% incidence of seriouscomplications were reported including 43 perforations. To minimize thisrisk, the operator must have a detailed familiarity with the regionalanatomy of the atrial septum. Due to the potentially life threateningcomplications of the procedure, many operators feel that fluoroscopy,which at best represents an epicardial shadow of the heart, is notenough and additional tools are needed. Additional techniques which maybe used to locate the fossa ovalis include biplane fluoroscopy, pressuremanometry, contrast infusion as well as surface, transesophageal orintracardiac echocardiography (i.e., ultrasound).

While echocardiography can be useful, there are potential problems inusing these techniques to locate the fossa ovalis. Contact of thetransseptal dilator and the tenting of the membrane of the fossa ovalisthat one looks for with echo guidance may be missed depending on thearea of the fossa that is cut by the ultrasound beam. If a differentportion of the membrane is tented by the dilator tip, this may not beapparent in the ultrasound picture. If transesophageal echocardiography(TEE) is used to guide the puncture, a different operator has to operatethe TEE system and therefore errors can occur especially in theinterpretation of the data. For example a different catheter (other thanthe transseptal dilator) may be tenting the fossa. Cardiac tamponade andother complications are known to have occurred during transseptalpunctures performed in electrophysiology laboratories despite theroutine use of ultrasound guidance. The placement and use of ultrasoundcatheters also often require the insertion of large intravascularsheaths. The additional time and expense that the use of ultrasoundcatheters and sheaths incurs is not inconsiderable and this can make itimpractical to use them routinely.

SUMMARY OF THE INVENTION

The present invention provides a method of identifying the fossa ovalisin a patient, comprising the steps of:

-   -   (a) positioning one or more electrodes against the tissue of the        interatrial septum of the patient;    -   (b) acquiring unipolar and/or bipolar electrograms of the tissue        of the interatrial septum, while moving the electrodes to a        plurality of positions against the tissue of the interatrial        septum; and    -   (c) identifying the fossa ovalis on the basis of at least one of        the following parameters:        -   unipolar voltage reduction        -   signal fractionation        -   broadened signal        -   reduced signal slew rate        -   reduced local myocardial impedance        -   increased phase angle and        -   increased pacing threshold.

The fossa ovalis may also be identified on the basis of bipolar voltagereduction. In addition, the fossa ovalis may be identified on the basisof at least two of the parameters noted above.

The present invention also provides a method of performing a transseptalpuncture on a patient, comprising the steps of:

-   -   (a) positioning one or more electrodes against the tissue of the        interatrial septum of the patient;    -   (b) acquiring unipolar and/or bipolar electrograms of the tissue        of the interatrial septum, while moving the electrodes to a        plurality of positions against the tissue of the interatrial        septum;    -   (c) identifying the fossa ovalis on the basis of at least one of        the following parameters:        -   unipolar voltage reduction        -   signal fractionation        -   broadened signal        -   reduced signal slew rate        -   reduced local myocardial impedance        -   increased phase angle and        -   increased pacing threshold    -   and    -   (d) penetrating the interatrial septum through the fossa ovalis        in order to access the left atrium.

In the above method, the one or more electrodes may be provided on thedistal end of a catheter and the positioning step may comprisepositioning the distal end of the catheter against the tissue of theinteratrial septum of the patient. In addition, the penetrating step maycomprise urging a needle through the interior of the catheter andthrough the fossa ovalis into the left atrium. This method may alsoinclude the step of observing ST segment elevation in the unipolarelectrogram in order to ensure that the distal end of the catheter is incontact with the tissue of the interatrial septum.

The present invention also provides a catheter for use in transseptalpunctures, comprising:

(a) a hollow lumen having a distal end;

(b) a first electrode positioned at the distal end; and

(c) a second electrode positioned on the catheter and spaced proximallyfrom the first electrode.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a light microscopy tissue section from a human atrial septum;

FIG. 2 is depicts the use of a quadripolar EP catheter to obtain bipolarelectrograms and identify the fossa ovalis on the basis of a decrease inamplitude as the catheter is dragged inferiorly along the interatrialseptum and makes contact with the fossa ovalis;

FIG. 3 depicts unipolar and bipolar electrograms taken from tissue ofthe interatrial septum adjacent the fossa ovalis and the fossa itself,with the fossa providing low voltage, broad and fractionated signalswith low slew rates;

FIG. 4 depicts unipolar and bipolar electrograms taken from tissue ofthe interatrial septum adjacent the fossa ovalis, wherein the unipolarelectrogram exhibits ST segment elevation while the bipolar electrogramdoes not, and the bipolar electrogram exhibits a low voltage even thoughthe probe was not at the fossa ovalis;

FIG. 5 is a schematic illustration of the significance of thepositioning of the interelectrode axis in bipolar electrograms withrespect to the orientation of the wavefront of electrical excitation;

FIG. 6 is similar to FIG. 4, however the location of the probe is shownto indicate that the bipolar electrogram exhibits reduced voltage eventhough the probe is not at the fossa ovalis;

FIG. 7 is a schematic illustration of a transseptal apparatus accordingto one embodiment of the present invention;

FIG. 8 is a cross-sectional view of the distal portion of the catheterof the transseptal apparatus shown in FIG. 7;

FIG. 9 is a schematic illustration of the use of the transseptalapparatus of FIG. 7 for obtaining unipolar electrograms, using a skinpatch as the indifferent (or reference) electrode;

FIG. 10 is a schematic illustration of the use of the transseptalapparatus of FIG. 7 for obtaining unipolar electrograms, using aWilson's central terminal as the indifferent electrode; and

FIG. 11 is a schematic illustration of the use of the transseptalapparatus of FIG. 7 for obtaining unipolar electrograms, using separateconventional EP catheter place in the inferior vena cava as theindifferent electrode.

DETAILED DESCRIPTION

Applicant has discovered that the fossa ovalis can be located bymeasuring electrophysiological activity of the tissue of the interatrialseptum. In addition, Applicant has also developed an apparatus which maybe used not only for locating the fossa ovalis, but also for performingtransseptal punctures through the fossa ovalis.

The fossa ovalis is the depression at the site of the fetal interatrialcommunication termed the foramen ovale. In fetal life, thiscommunication allows richly oxygenated IVC blood coming from theplacenta to reach the left atrium and has a well-marked rim or limbussuperiorly. The floor of the fossa ovalis is a thin, fibromuscularpartition. In fact, because the fossa ovalis is thinner than the rest ofthe interatrial septum, light may even be used to selectivelytransilluminate the fossa ovalis.

However, in addition to being thinner than the surrounding tissue of theinteratrial septum, Applicant has discovered that the fossa ovalis hasconsiderable scar tissue. Autopsy studies done on human hearts (withMasson trichrome stain and microscopy/morphometric analysis with NIHimage program) revealed that the fossa ovalis has significantly morefibrous tissue that the non fossa portion of the interatrial septum.Specifically, the non fossa portion of the interatrial septumconsistently had around 70% muscle and 30% fibrous tissue, whereas thefossa ovalis had an average of 33% muscle and 67% fibrous tissue.

FIG. 1 is a light microscopy tissue section from a human atrial septumwith hematoxylin & eosin staining (panels A, C & E) as well as Massontrichrome stain (panels B, D & F). Panels A & B show the superior limbusas well as the membrane of the fossa ovalis. Panels C & D show thesuperior limbus of the interatrial septum, while panels E & F show themembrane of the fossa ovalis. As noted from FIG. 1, the fossa ovalis hassignificantly more fibrous scar tissue than other portions of theinteratrial septum. Applicant has found that this increased scar tissue,coupled with the reduced thickness of the fossa ovalis, allows one tolocate the fossa by measuring electrophysiological activity of theregion.

In particular, Applicant has found that the fossa ovalis may be locatedby measuring the electrophysiological (“EP”) activity of the fossaovalis and surrounding heart tissue. By observing differences in the EPactivity of tissue at various locations, the operator may determine thelocation of the fossa ovalis. The lower muscle content and higherfibrous tissue content of the fossa ovalis with respect to the rest ofthe interatrial septum, as well as the relative “thinning” of the fossa,results in changes in EP activity which may be readily observed via anintracardiac electrogram. For example, the fossa ovalis will recordbroader, fractionated electrograms of lower amplitude and lower slewrates. Based upon these surprising findings, one or more electrodes foracquiring EP data may be incorporated into a catheter/dilator usedduring transseptal puncture.

Intracardiac electrograms are typically performed by positioning a probehaving one or more electrodes against the cardiac tissue to be examined.The probe is typically inserted into the heart through a vein or arteryvia a sheath. A recording device (well-known to those skilled in theart) is used to record and display an electrical signal produced by thecardiac tissue. When a unipolar probe is used, the lead from the singleelectrode on the probe is connected to the positive terminal of arecording device or amplifier, and an indifferent (or reference)electrode is then connected to the negative terminal of the recordingdevice or amplifier. The indifferent electrode is simply anotherelectrode which is located away from the “exploring” electrode—typicallypositioned within or against a structure in which no electrical activitytakes place. The reference electrode may comprise a skin patch, aplurality of electrodes placed at various locations on the patient'sbody (i.e., Wilson's central terminal), or even an electrode placed in aseparate catheter positioned in a large vein (e.g., the inferior venacava). For unipolar electrograms, the electrogram will display thedifference in electrical potential between the unipolar electrodepositioned against the cardiac tissue and the electrode connected to thenegative electrode.

For bipolar electrograms, the probe typically comprises two electrodesspaced apart from one another by a short distance (typically less thanabout 5 mm) in a single probe. The leads from the two electrodes areconnected to a junction box of a recording device.

A signal in an intracardiac electrogram is characterized in terms of itsamplitude (typically measured in millivolts), its duration (measured inmilliseconds) and its slew rate (measured in volts per second). Theamplitude of an electrogram depends on several factors, including themass of myocardium underlying the electrode, the contact of theelectrode with the myocardium, the orientation of the electrode withrespect to the axis of depolarization, and the presence of anyinexcitable tissue (i.e., fibrous or connective tissue) between themyocytes and the electrode. Electrodes that are in contact withinfarcted ventricular myocardium or those that have become encapsulatedwith a thick layer of fibrous tissue, for example, typically show alower amplitude electrogram than those directly in contact with healthymyocytes. The slew rate represents the maximal rate of change of theelectrical signal between the sensing electrodes and, mathematically, isthe first derivative of the electrogram (dv/dt) and is a measure of thechange in electrogram voltage over time. It is generally directlyrelated to the electrogram amplitude and duration. In the region of thefossa ovalis, the slew rate will be lower in the region of the fossaovalis, thus following the changes in electrogram amplitude.

FIG. 2 depicts a bipolar electrogram acquired using a standard EPdeflectable catheter 30. In FIG. 2, quadripolar EP catheter 30 islocated within the right atrium, against the interatrial septum abovethe fossa ovalis 25 (see FIG. 2A). For point of reference, the superiorvena cava is depicted at 21, the aorta at 22, the pulmonary artery at 23and the coronary sinus at 24. As the catheter 30 is dragged inferiorlyalong the interatrial septum and makes contact with the fossa ovalis 25(FIG. 2B), the bipolar electroanatomical voltage 31 drops abruptly. Infact, the region of the fossa ovalis consistently displays unipolar andbipolar electrograms of amplitudes less than about 1 mV while the restof the interatrial septum displays electrograms greater than about 2 mV(see FIG. 3).

High density mapping of the interatrial septum (performed with the CARTOsystem available from Biosense Webster, Diamond Bar, Calif.) furtherrevealed that the area of the fossa ovalis (posterior to the coronarysinus ostium and inferior to the His bundle) consistently shows lowvoltage and fractionated unipolar and bipolar electrograms. FIG. 3depicts bipolar and unipolar electrograms obtained using the CARTOsystem. Panel A of FIG. 3 depicts bipolar and unipolar electrograms fora location on the interatrial septum superior to the fossa ovalis. Asnoted in panel A of FIG. 3, the unipolar voltage is 2.66 mV and thebipolar voltage is 2.52 mV. Panel B of FIG. 3 depicts bipolar andunipolar electrograms for the fossa ovalis 25. As noted in panel B ofFIG. 3, the unipolar voltage for the fossa ovalis is 0.52 mV and thebipolar voltage is 0.84 mV. Thus, the drop in voltage for the fossaovalis as compared to the surrounding tissue of the interatrial septummay be effectively used to locate the fossa ovalis.

As seen in FIG. 3, the region of the fossa ovalis also displayselectrograms that are broad (greater than about 50 ms in duration) whilethe rest of the interatrial septum has signals that are less than about35 ms in width. Bipolar electrograms also show multiple spikes ordeflections (fractionation), and the unipolar electrogram is broad witha low slew rate. This fractionation in the electrogram morphology isthought to be due to the substantially greater amounts of collagen inthis tissue compared to the rest of the atrium resulting in complexanisotropic conduction. With respect to the slew rate in unipolarelectrograms, the slew rate observed for the fossa ovalis is less thanor equal to about 0.3 volts/second, whereas the rest of the interatrialseptum provides slew rates of greater than about 0.5 volts/second. Thus,the increased fractionation, increased signal width and decreased slewrate provide additional indicia of the location of the fossa ovalis.

Not only can the fossa ovalis be identified by observing reduced signalamplitude, and increased width, fractionation and slew rate, the fossawill also be evidenced by reduced local myocardial impedance and higherphase angle. Myocardial tissue impedance is considered to be a passiveelectrical property of both healthy and diseased tissues. The myocardialimpedance (Z) is defined as the voltage (V) divided by the sinusoidalcurrent (I) applied through it. It has been noted by severalinvestigators that ventricular aneurysms from chronic myocardialinfarctions display a lower local myocardial impedance measurement and ahigher phase angle. Changes in impedance measurements were found to bereliable in identifying scar tissue and in defining the presence, extentand location of chronic myocardial infarction. The lower endocardialimpedance values in scar tissues is thought to be due to an increase inthe extracellular-to-intracellular volume ratio and a resultant increasein the extracellular pathways of impulse conduction. Another hypothesisis that the improved conductance may be due to the thinning of the leftventricular wall and loss of cardiac tissue mass.

Applicant has found that the lower muscle content and higher fibroustissue content of the fossa with respect to the rest of the interatrialseptum as well as the relative “thinning” of the fossa ovalis willresult in the recording of lower local impedance values and thus can beused to identify the fossa ovalis. When the catheter is positioned inthe superior vena cava, the system generally recorded impedance valuesof greater than about 130 ohms. Once the catheter descended into theright atrium, the impedance decreased to about 120 ohms or less.Dragging the catheter to the region of the fossa ovalis lowered theimpedance value by about another 15 ohms. Therefore, by observing themyocardial impedance as the tip of the catheter or other probe isdragged inferiorly across the interatrial septum, the fossa ovalis alsocan be identified by a sharp drop in impedance (typically about 15ohms). Similarly, the fossa ovalis can also be identified by an increasein phase angle as compared to the surrounding tissue.

Impedance may be measured, for example, using the technique described byWolf et al, Am. J. Physiol. 2001; 280: H179-H188. A generator (such as aStockert generator, available from Biosense Webster, Diamond Bar,Calif.) with a stabilized output amplitude, and producing a sine wavesignal of 1-2 uA with a frequency of 50 kHz, is used. The output currentsource buffer with a high output impedance is connected to anintracardiac electrode and provided constant alternating current throughthe myocardial tissues. A return electrode is connected to the referencepoint in the circuit and placed against the patient's back. Theintracardiac electrode is connected to one input of a differentialamplifier and the return electrode is connected to the second input. Theoutput of the amplifier is then passed through a band pass filter with acentral frequency equal to the measuring frequency. A synchronousdetector converts the AC voltage to the direct current.

The presence of greater amounts of fibrous tissue in the fossa ovaliswill also result in a higher pacing threshold and thus, will serve as anadditional electrophysiological measurement in identifying the fossaovalis. “Pacing threshold” refers to the amount of current from apacemaker electrical impulse required to capture the heart. It isheavily dependent on the amount of muscle and scar/fibrous tissue thatthe pacing catheter is in contact with. The more scar/fibrous tissuethat is present, the higher the pacing threshold.

Thus, an electrical pacing impulse may be applied to the interatrialseptum through an electrode (e.g., a standard EP deflectable catheter oreven an electrode on the transseptal apparatus of the present inventiondescribed further herein). The minimum amplitude required to capture theheart is applied and the probe or catheter carrying the electrode isdragged inferiorly across the interatrial septum. As the electrodereached the fossa ovalis, the electrical impulse will no longer be ofsufficient amplitude to capture the heart. For example, an electricalimpulse having a pulse width duration of about 0.5 msec and an amplitudeof between about 0.8 and about 1.0 V will generally be sufficient tocapture the hear when applied to the interatrial septum adjacent thefossa ovalis. However, this amplitude will not be sufficient to capturethe heart when applied to the fossa ovalis. Here, an amplitude ofbetween about 1.5 and about 1.6 V is required, at a pulse width durationof 0.5 msec. Thus, the increased pacing threshold may also be used tolocate the fossa ovalis.

In addition the various parameters described above for locating thefossa ovalis, the ST segment elevation observed in unipolar electrogramscan also be advantageously employed during transseptal puncture. Theunipolar electrogram of the tissue of the interatrial septum willdisplay ST segment elevation whenever the electrode makes good tissuecontact with, and exerts significant pressure against the atrialmyocardium. As seen in FIG. 4, ST segment elevation is recorded in theunipolar electrogram of the interatrial septum but not the bipolarelectrogram. By observing ST segment elevation, the operator can beconfident that the catheter is exerting significant pressure on themyocardium for transseptal puncture (via a needle passed through thecatheter).

The above mentioned electrophysiological parameters can be used to guidethe transseptal puncture procedure. For example, a single electrode maybe incorporated into the tip of the dilator of the transseptal apparatus(to record unipolar electrograms and other electrophysiologicalparameters). Alternatively, a pair of electrodes may be incorporatedinto the dilator in order to measure bipolar electrograms. Because thereare several electrophysiological distinctions between the fossa ovalisand the rest of the atrial myocardium, the use of multipleelectrophysiological parameters will add to the predictive value of themeasurements made by the apparatus.

Although bipolar electrograms can be useful in locating the fossaovalis, bipolar electrograms have a serious flaw in that if thewavefront of electrical activity travels in a direction perpendicular tothe interelectrode axis, no electrical activity may be recorded. Giventhe potential for life threatening complications if a transseptalpuncture were to be made in the wrong area of the atrium, this canliterally be a fatal flaw if one were to rely solely on voltagemeasurements taken from bipolar electrograms. The electrophysiologicalbasis for this flaw and other advantages of unipolar electrograms arediscussed below.

Potentials generated by current sources in a volume conductor such asthe heart are always recorded with respect to the potential at areference site. Thus, it is the difference in electrical potentialbetween the two electrodes produced by electrical currents within themyocardium that generates the intracardiac electrogram. In practice, thesignal at the recording site is fed into the positive input and thereference signal into the negative input of a recording device.

A bipolar electrogram can be considered to be the instantaneousdifference in potential between two unipolar electrograms recorded fromtwo unipolar electrodes and a common remote indifferent electrode. Inmathematical terms, the bipolar electrogram is equal to the unipolarelectrogram from first electrode 35 minus the unipolar electrogram fromsecond electrode 36. In other words:BiEGM=UniEGM1−UniEGM2.If the unipolar tip and ring electrograms have similar amplitude andtiming, the two signals will cancel each other out and the resultingbipolar electrogram will be nonexistent or much smaller than eitherunipolar electrogram alone.

Because of this, bipolar electrograms are susceptible to the orientationof the interelectrode axis with respect to the depolarizing wavefront.As shown in panels A and B of FIG. 5, if the axis of the elongate probe(i.e., the interelectrode axis) is parallel to the direction in whichthe depolarizing wavefront is advancing, a sharp electrogram will beinscribed. However, if the interelectrode axis is perpendicular to thewavefront (panels C and D of FIG. 5), as the wavefront passes underneaththem, the shift in potential beneath the two electrodes will beidentical. The electrodes in this scenario, will record no difference inelectrical potential with respect to each other. Consequently, nointracardiac electrogram is generated. In general, it is recognized thatbipolar electrograms are a function of three variables: the voltage ofthe tip or distal electrode, the voltage of the ring or proximalelectrode, and the presence of activation time difference (phase shift)between the poles or electrode. This is in contrast with unipolarelectrograms where the only variable is the voltage of the tipelectrode. Due to the increased number of variables, the greatervariance in bipolar electrograms is not surprising. The large signalvariation associated with normal respiration often seen with bipolarelectrograms is additional evidence for their inconsistency.

A dramatic illustration of the potential problems associated withrelying on bipolar electrograms alone is shown in FIG. 6 which depicts afalse reading of low voltage by bipolar electrogram. Here, a catheter 34having first and second electrodes 35 and 36 is positioned such that thecatheter tip (and hence both electrodes) are positioned in the posteriorwall of a human atrium away from the fossa ovalis. A transseptalpuncture performed at this site can have life threatening complications.However, the bipolar electrogram from this site indicates a voltage ofonly 0.95 mV, while the unipolar electrogram exhibits a voltage of 2.43mV (indicating that the tip of the catheter is not at the fossa ovalis).This discrepancy is more than likely the result of unipolar EGMsrecorded by the distal and proximal electrodes of the catheter being ofsimilar amplitude and that there is no significant phase shift in timingof activation. Thus, the voltage of the bipolar electrogram signalshould not be relied upon, by itself, to locate the fossa ovalis.

The principles and sensing configuration described above, i.e. recordingof electrical signals from a pair of electrodes both of which are incontact with the myocardium, describe the bipolar system. In the bipolarrecording mode, the reference electrode is positioned close to theexploring electrode. In the unipolar mode, the reference electrode(usually the anode) is located at an infinite distance from therecording site (cathode). Theoretically, the reference electrode islocated beyond the zone of current flow that generates the electricalfield at the exploring electrode. Therefore, a unipolar recording mayreflect influences from both local and distant electrical events.Unipolar electrograms recorded from the heart may include activity fromother parts of the heart, although their contribution decreases withdistance. Simultaneous recordings of intra- and extracellularelectrograms have shown that for the downstroke of the unipolarelectrogram, the intrinsic deflection coincides with the upstroke of theaction potential beneath the exploring electrode.

In clinical practice, during the recording of unipolar electrograms withpacemakers, the pulse generator functions as the reference electrode. Inthe electrophysiology laboratory, the reference electrode is usually oneof the following:

a) Skin patch: A wire is connected to the skin patch and leads to thenegative terminal of the amplifier. During implantation of unipolarpacemaker leads, the lead is often tested with an alligator clipconnected to muscle in the exposed pocket and the other end connected tothe negative terminal of the amplifier (using the same principle as theskin patch).

b) Wilson's central terminal: Central terminal created by connecting allthree limb electrodes through a 5000 ohm resistor. This terminal is usedas the negative pole.

c) Indifferent electrode in one of the great veins such as the inferiorvena cava: A separate catheter that is connected to the negative inputof the amplifier may also be placed in one of the great veins.

Investigators have found that the peak to peak amplitude of the unipolarsignal correlated quantitatively with local histologic ischemic changesin the setting of ischemic cardiac injury. In patients with cardiacscars and aneurysms from prior myocardial infarctions, voltage mappingwith unipolar electrograms reliably differentiates normally perfusedmyocardium from fixed perfusion defects, and also identifies non-viablezones within the perfusion defects. In the study by Keck et al, theunipolar voltage findings correlated well with findings from PositronEmission Tomography (PET) glucose utilization. Bipolar electrograms areoften difficult to interpret especially when the signals arefractionated (when they have multiple deflections). In contrast, theinterpretation of the unipolar electrogram is straightforward, evenunder abnormal conditions and this feature is its great strength.

FIGS. 7 and 8 depict a transseptal apparatus 50 according to the presentinvention which may be used to not only locate the fossa ovalis but alsoto perform a transseptal puncture. Transseptal apparatus 50 is similarto conventional transseptal apparatus in that it includes a hollowsheath 51 and an internal catheter (sometimes referred to as a dilator)52. Catheter 52 is hollow and is slightly longer than sheath 51(typically about 4 cm longer). As is known to those skilled in the art,a guidewire is inserted through the right femoral vein and advanced tothe superior vena cava. Catheter (or dilator) 52 is inserted into sheath51, with the distal end of the catheter protruding beyond the distal end56 of sheath 51. The sheath and catheter are then advanced over theguidewire into the superior vena cava. The guidewire is then removed.

Not only is the distal end 70 of catheter 52 tapered in the conventionalmanner, a pair of electrodes 65 and 66 are provided at the distal end ofcatheter 52. First, or distal, electrode 65 is provided at the tip ofcatheter 52, and second, or proximal, electrode 66 may also be providedat the distal end of catheter 52, spaced proximally from first electrode65 by a distance of between about 2 and about 4 mm. The electrodes may,for example, be ring-shaped, with the first electrode measuring betweenabout 2 mm and about 4 mm in length, and the second electrode measuringabout 2 mm in length. Electrical leads 73 and 74 are in electricalcommunication with first and second electrodes 65 and 66, respectively.At the proximal end of catheter 52, electrical leads 73 and 74 are inelectrical communication with cables 53 and 54, respectively, which maybe attached to a differential amplifier or other device for generatingelectrograms. In this manner, the tip portion 70 of catheter 52 willfunction as an electrophysiology mapping catheter (both bipolar andunipolar), and will also serve the same function as a catheter/dilatorin a conventional transseptal apparatus.

FIGS. 9-11 depict the use of transseptal apparatus 70 in a transseptalpuncture using unipolar electrograms to locate the fossa ovalis. Sinceonly unipolar measurements are depicted, the second electrode has beenomitted from the tip 70 of catheter 52. However, it should be notedthat, even if second electrode 66 is provided on catheter 52, thecatheter can still be used for unipolar (as well as bipolar)measurements. In FIG. 9, transseptal apparatus 50 has been inserted intothe patient's femoral vein until the distal tip 70 of thecatheter/dilator is located within superior vena cava. The electricallead from electrode 65 on tip 70 is used as the positive input to adifferential amplifier, while a skin patch 75 serves as the referenceelectrode and is attached to the negative input to the differentialamplifier via a wire or other lead. Distal tip 70 having first electrode65 is then dragged inferiorly along the interatrial septum while theoperator monitors the electrophysiological parameters for indicationthat the distal tip 70 has made contact with the fossa ovalis. One ormore of the indicators described previously may be employed to make thisdetermination. In addition, the operator may also observe ST segmentelevation in order to confirm that the distal tip 70 is exertingsignificant pressure against the fossa ovalis.

Once the operator has confirmed the location of the fossa ovalis andthat the distal tip 70 is in good contact with the fossa ovalis, aneedle may be urged through the central lumen of catheter 52 until thetip of the needle protrudes beyond distal tip 70 through the fossaovalis and into the left atrium. Thereafter, the catheter 52 may beurged through the fossa ovalis, followed by sheath 51. The catheter 52and needle are then removed from sheath 51, leaving sheath 51 extendingthrough the fossa ovalis into the left atrium.

FIG. 10 depicts an alternative arrangement wherein the Wilson's centralterminal is used as the reference electrode. Wilson's central terminalis created by connecting all three limb electrodes through a 5000 ohmresistor. This terminal is used as the negative pole.

FIG. 11 depicts yet another alternative arrangement wherein anindifferent electrode 76 is positioned in the inferior vena cava. Aseparate catheter that is connected to the negative input of theamplifier may also be placed in one of the great veins.

1-11. (canceled)
 12. A method of identifying the fossa ovalis in apatient, the method comprising: (a) positioning one or more electrodesagainst the tissue of the interatrial septum of the patient; (b)acquiring unipolar and/or bipolar electrograms of the tissue of theinteratrial septum, while moving the one or more electrodes to aplurality of positions against the tissue of the interatrial septum; and(c) identifying the fossa ovalis on the basis of at least one of thefollowing parameters: unipolar voltage reduction, signal fractionation,broadened signal, reduced signal slew rate, reduced local myocardialimpedance, increased phase angle and increased pacing threshold.
 13. Themethod of claim 12, wherein the fossa ovalis is also identified on thebasis of bipolar voltage reduction.
 14. The method of claim 12, whereinthe fossa ovalis is identified on the basis of at least two of thefollowing parameters: unipolar voltage reduction, signal fractionation,broadened signal, reduced signal slew rate, reduced local myocardialimpedance, increased phase angle and increased pacing threshold.
 15. Amethod of performing a transseptal puncture on a patient, the methodcomprising: (a) positioning one or more electrodes against the tissue ofthe interatrial septum of the patient; (b) acquiring unipolar and/orbipolar electrograms of the tissue of the interatrial septum, whilemoving the one or more electrodes to a plurality of positions againstthe tissue of the interatrial septum; (c) identifying the fossa ovalison the basis of at least one of the following parameters: unipolarvoltage reduction, signal fractionation, broadened signal, reducedsignal slew rate, reduced local myocardial impedance, increased phaseangle and increased pacing threshold; and (d) penetrating theinteratrial septum through the fossa ovalis in order to access the leftatrium.
 16. The method of claim 15, wherein the one or more electrodesare provided on the distal end of a catheter and the positioning stepcomprises positioning the distal end of the catheter against the tissueof the interatrial septum of the patient.
 17. The method of claim 16,wherein penetrating the interatrial septum comprises urging a needlethrough the interior of the catheter and through the fossa ovalis intothe left atrium.
 18. The method of claim 16, wherein two electrodes areprovided on the catheter, one of the one or more electrodes at thedistal end of the catheter and the other of the one or more electrodesis located on the catheter proximal to the other electrode.
 19. Themethod of claim 16, wherein a bipolar and unipolar electrograms areacquired and the method further comprising observing ST segmentelevation in the unipolar electrogram in order to ensure that the distalend of the catheter is in contact with the tissue of the interatrialseptum.
 20. The method of claim 15, wherein the fossa ovalis is alsoidentified on the basis of bipolar voltage reduction.
 21. The method ofclaim 15, wherein the fossa ovalis is identified on the basis at leasttwo of the following parameters: unipolar voltage reduction, signalfractionation, broadened signal, reduced signal slew rate, reduced localmyocardial impedance, increased phase angle and increased pacingthreshold.
 22. The method of claim 12, wherein the fossa ovalis isidentified on the basis of unipolar voltage reduction.
 23. The method ofclaim 15, wherein the fossa ovalis is identified on the basis ofunipolar voltage reduction.
 24. The method of claim 15, furthercomprising positioning at least one indifferent electrode within oragainst the patient such that the at least one indifferent electrode maybe used in conjunction with one of the one or more electrodes positionedagainst the interatrial septum in order to acquire unipolarelectrograms.
 25. The method of claim 24, wherein the at least oneindifferent electrode is chosen from the group consisting of: a skinpatch, a Wilson's central terminal, and an electrode positioned in avein of the patent.
 26. The method of claim 17, further comprising thesteps of: inserting a guidewire through a femoral vein of the patientand advancing the guidewire to the superior vena cava; inserting thecatheter into a sheath; advancing the sheath and the catheter over saidguidewire into the superior vena cava in order to position the distalend of the catheter against the interatrial septum; after penetratingthe interatrial septum, urging the catheter and the sheath through thefossa ovalis into the left atrium; and after the sheath has been urgedthrough the fossa ovalis, removing the catheter and the needle from thesheath.